Unlocking the mysteries of Alzheimer’s

Bennett Steffany

“We argue that not all of the mysteries of life lie in our genetic code. Some can be found buried in our cellular membranes.”

– Steffany Bennett

The heightened neural activity and brightness of manner that Bennett exhibits in such moments are in sharp contrast to the effects of Alzheimer’s disease, the devastating and all-too-common condition that sharply erodes a sufferer’s memory, personality and everyday functioning.

Alzheimer’s affects some 24.3 million people in North America alone, and the most daunting aspect of the disease may be the relative scar­city of treatment options, which really only delay the inevitable.

“Alzheimer’s is such an insidious disease with a slow progression, so that the brain is able to adapt and mask the symptoms for a very long period of time,” says Bennett in a more sober moment. “We do not show any symptoms until a great deal of damage has already been done. Prevention and resistance are the keys to fighting this devastating disorder.”

In a quest for earlier identification of Alzheimer’s and to find more effective treatments, Bennett heads up two integrated research programs that together give her one of the most expansive and well-equipped networks in her field of neurodegenerative lipidomics.

Bennett’s Neural Regeneration Laboratory (NRL) at the Ottawa Institute of Systems Biology is part of a rare network of laboratories located as close to home as Carleton University and the universities of Toronto and Montréal, and as far afield as Harvard University, Nashville’s Vanderbilt University and the University of Bonn in Germany.

How does Bennett continue to bring new blood into this research network?

“With the support of the Canadian Institutes of Health Research, I am very fortunate to lead a new training program in neurodegenerative lipidomics with 18 research scientists and 53 trainees at uOttawa, Carleton University, the University of Toronto and the Sunnybrook Health Centre, under the auspices of the Ottawa Institute of Systems Biology.”

Though Bennett’s programs integrate diverse fields, the bulk of the core research is focused on one key area: lipid metabolism, the building blocks of biological membranes.

“We argue that not all of the mysteries of life lie in our genetic code,” explains Bennett. “Some can be found buried in our cellular membranes.”

“The diversity of neural structural lipids, coupled with their chameleon-like capacity to shape-shift from one identity to another, allows for hundreds of immediate signalling responses,” Bennett continues. “So, because each person has a different coating of brain fat at any given moment, based on our metabolism, our diet and our genetic makeup, this composition could render us susceptible or resistant to neurodegenerative disease from moment to moment.”

Noting how the Alzheimer’s research community has made remarkable strides in identifying potential genetic and environmental risk factors, Bennett also points out how many of these risk factors modulate lipid metabolism in the brain.

“How these small fat molecules are modified likely impacts upon our ability to resist the disease,” Bennett argues. “Initially, memory dys­function is reversible in Alzheimer’s. Confused and disoriented patients can revert to being alert and coherent within minutes. This ability to return to oneself raises hope, as it suggests a metabolic component to early synaptic dysfunction that has only just begun to be explored.”

Bennett’s visible excitement returns when she discusses an important paper her team published in the Proceedings of the National Academy of Science—“one of the first to come out of our interdisciplinary team approach,” she says.

The paper brings together unique expertise in cell biology, analytical chemistry, animal physiology, enzymology and medicine, examining how lipids bridge the gap between the two known pathologies of Alzheimer’s.

“We are very excited by the findings that the amyloid depositions that form in Alzheimer’s alter the production of a small lipid molecule called PC(O-16:0/2:0) PAF,” Bennett explains. “When levels of this lipid are too high in brain cells, the lipid itself signals the cell to alter the other hallmark of Alzheimer’s, the protein tau. We found that preventing the accumulation of this small lipid was sufficient to pre­vent these changes.”

“We are excited because this work provides proof of the principle that targeted intervention in lipid metabolism has a real impact on Alzheimer’s pathology. We are testing now in animals to see if this intervention can prevent the loss of memory that defines this devas­tating disease. This is not just the work of one person’s laboratory. This is all of us working together to make a difference.”

 

by Tony Martins

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